De Waal E J, Rademakers L H, Schuurman H J, Vos J G, Van Loveren H
National Institute of Public Health and The Environment, Bilthoven, The Netherlands.
Toxicology. 1996 Jun 17;110(1-3):133-51. doi: 10.1016/0300-483x(96)03332-x.
After cyclosporine treatment, dendritic cells disappear from the rat thymic medulla. The present study was undertaken to examine the ultrastructural alterations in the dendritic cell population during 14-day cyclosporine treatment and subsequent 6-week recovery. Four dendritic cell subtypes were defined ultrastructurally by a newly developed classification system. In addition, the potential effect of cyclosporine on six medullary epithelial cell subtypes was studied. During cyclosporine treatment, a prominent reduction of dendritic cells was seen at the ultrastructural level, whereas the total number of medullary epithelial cells remained largely unchanged. These findings were confirmed by immunohistochemistry. The number of mature dendritic cells declined later than the number of immature ones. A decrease in the antigen-processing capacity of remaining dendritic cells was suggested by the disappearance of Birbeck granules and the reduced number of tubulovesicular complexes. These findings support a disturbance of clonal deletion during cyclosporine treatment. The dendritic cell alterations appeared reversible 4 weeks after the restoration of the original architecture. During recovery, dendritic cells displaying lysosomal elements outnumbered those found in the normal uninvoluted thymus. This phenomenon probably reflects an enhanced turnover of cell organelles. No treatment-related effect on epithelial cell subtypes was seen.
环孢素治疗后，树突状细胞从大鼠胸腺髓质消失。本研究旨在检测环孢素治疗14天及随后6周恢复期间树突状细胞群体的超微结构变化。通过新开发的分类系统在超微结构上定义了四种树突状细胞亚型。此外，还研究了环孢素对六种髓质上皮细胞亚型的潜在影响。在环孢素治疗期间，超微结构水平上可见树突状细胞显著减少，而髓质上皮细胞总数基本保持不变。这些发现通过免疫组织化学得到证实。成熟树突状细胞数量的减少比未成熟树突状细胞晚。伯贝克颗粒的消失和管状囊泡复合体数量的减少提示剩余树突状细胞的抗原处理能力下降。这些发现支持环孢素治疗期间克隆清除受到干扰。在恢复到原始结构4周后，树突状细胞的改变似乎是可逆的。在恢复期间，显示溶酶体成分的树突状细胞数量超过正常未退化胸腺中的数量。这种现象可能反映了细胞器更新的增强。未观察到对上皮细胞亚型的治疗相关影响。
